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Pharmacology and TherapeuticsPharmacology and TherapeuticsPharmacology and TherapeuticsPharmacology and Therapeutics
A.Q. Sangalang, MD, FPOGSA.Q. Sangalang, MD, FPOGSFACULTY OF PHARMACYFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMASUNIVERSITY OF SANTO TOMAS
A.Q. Sangalang, MD, FPOGSA.Q. Sangalang, MD, FPOGSFACULTY OF PHARMACYFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMASUNIVERSITY OF SANTO TOMAS
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
PHARMACOLOGYPHARMACOLOGY
Body of knowledge concerned with the action Body of knowledge concerned with the action of chemicals on biologic systems, especially by of chemicals on biologic systems, especially by binding to regulatory molecules (binding to regulatory molecules (receptorsreceptors) and ) and activating or inhibiting normal body processesactivating or inhibiting normal body processes
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
MEDICAL PHARMACOLOGYMEDICAL PHARMACOLOGY
Area of pharmacology concerned with the use of chemicals in the prevention, diagnosis,
and treatment of disease, especially in humans
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
TOXICOLOGYTOXICOLOGY
Area of pharmacology concerned with theArea of pharmacology concerned with the undesirable effects of chemicals on undesirable effects of chemicals on
biologic systemsbiologic systems
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
MOLECULAR BIOLOGYMOLECULAR BIOLOGY
Identifies the exact mechanism of action Identifies the exact mechanism of action of one particular drug of one particular drug
Identifies the receptorsIdentifies the receptors
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
DRUGDRUG
Any substance that brings about a change Any substance that brings about a change in biologic function through chemical actionsin biologic function through chemical actions
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
RECEPTORRECEPTOR
Specific molecule in the biologic system that Specific molecule in the biologic system that plays a regulatory roleplays a regulatory role
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
THE NATURE OF DRUGSTHE NATURE OF DRUGS
Inorganic ions, nonpeptide organic molecules, Inorganic ions, nonpeptide organic molecules, small peptides and proteins, nucleic acids, small peptides and proteins, nucleic acids, lipids, and carbohydrateslipids, and carbohydrates
Found in plants or animals, many are partially or Found in plants or animals, many are partially or completely syntheticcompletely synthetic
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
PHYSICAL NATURE OF DRUGSPHYSICAL NATURE OF DRUGS SolidSolid LiquidLiquid GasGas
Drugs are given at a site distant from the Drugs are given at a site distant from the
intended site of actionintended site of action
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
DRUG SIZE AND MOLECULAR WEIGHTDRUG SIZE AND MOLECULAR WEIGHT (MW)(MW)
Vary in size Vary in size MW 7MW 7 (lithium) (lithium) MW 50,000MW 50,000 (thrombolytic agents) (thrombolytic agents)
Majority have Majority have MWMW between between 100 100 and and 10001000
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
DRUG SIZE AND MOLECULAR WEIGHTDRUG SIZE AND MOLECULAR WEIGHT (MW)(MW)
100 MW100 MW For selective bindingFor selective binding
1000 MW1000 MW For traversing to different barriers of the bodyFor traversing to different barriers of the body
>1000 MW>1000 MW Cannot move within the bodyCannot move within the body Given directly at the site of actionGiven directly at the site of action
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
DRUG RECEPTOR BONDSDRUG RECEPTOR BONDS
Chemical forces or bonds through Chemical forces or bonds through which the drug interacts with the which the drug interacts with the receptorsreceptors
Weaker bonds are more selective Weaker bonds are more selective bondsbonds
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
DRUG RECEPTOR BONDSDRUG RECEPTOR BONDS
COVALENT BONDSCOVALENT BONDS StrongestStrongest IrreversibleIrreversible
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
DRUG RECEPTOR BONDSDRUG RECEPTOR BONDS
ELECTROSTATIC BONDSELECTROSTATIC BONDS More commonMore common Weaker Weaker Eg, between cation and an anionEg, between cation and an anion
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
DRUG RECEPTOR BONDSDRUG RECEPTOR BONDS
HYDROPHOBIC BONDSHYDROPHOBIC BONDS WeakestWeakest Highly lipid soluble drugsHighly lipid soluble drugs
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
THE MOVEMENT OF DRUGS IN THE THE MOVEMENT OF DRUGS IN THE
BODYBODY To reach its receptors and bring about biologic To reach its receptors and bring about biologic
effecteffect A drug molecule (eg, sedative) must A drug molecule (eg, sedative) must
travel from the site of administration travel from the site of administration
(eg, gastrointestinal tract) to the site (eg, gastrointestinal tract) to the site
of action (eg, brain)of action (eg, brain)
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
A.A. PERMEATIONPERMEATION
Movement of drug molecules into and withinMovement of drug molecules into and within the biologic environmentthe biologic environment
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
A.A. PERMEATIONPERMEATION1.1. AQUEOUS DIFFUSIONAQUEOUS DIFFUSION Movement of molecules through the watery Movement of molecules through the watery
extracellular and intracellular spacesextracellular and intracellular spaces Membranes of capillaries with small water- Membranes of capillaries with small water-
filled poresfilled pores Passive processPassive process Governed by Fick’s law Governed by Fick’s law
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
A.A. PERMEATIONPERMEATION2.2. LIPID DIFFUSIONLIPID DIFFUSION Movement of molecules through membranesMovement of molecules through membranes
and other lipid structuresand other lipid structures Most important factor for drug permeationMost important factor for drug permeation
Large lipid barriers that separate theLarge lipid barriers that separate thecompartments of the bodycompartments of the body
Passive process Passive process Governed by Fick’s lawGoverned by Fick’s law
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
A.A. PERMEATIONPERMEATION3.3. TRANSPORT BY SPECIAL CARRIERSTRANSPORT BY SPECIAL CARRIERS Drugs transported across barriers by Drugs transported across barriers by
mechanisms that carry similar endogenousmechanisms that carry similar endogenous
substances substances Amino acid carriers, weak acid carriersAmino acid carriers, weak acid carriers
Capacity limitedCapacity limited Not governed by Fick’s lawNot governed by Fick’s law
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
A.A. PERMEATIONPERMEATION
3.3. TRANSPORT BY SPECIAL CARRIERSTRANSPORT BY SPECIAL CARRIERS
ACTIVE TRANSPORTACTIVE TRANSPORT Needs energyNeeds energy Against a concentrationAgainst a concentration gradientgradient
FACILITATED DIFFUSIONFACILITATED DIFFUSION No energy requiredNo energy required DownhillDownhill
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
A.A. PERMEATIONPERMEATION4.4. ENDOCYTOSISENDOCYTOSIS Binding to specialized components Binding to specialized components
(receptors) on cell membranes(receptors) on cell membranes Internalization by infolding of the area of Internalization by infolding of the area of
the membrane and contents of the vesicle the membrane and contents of the vesicle
are subsequently released into the cytoplasmare subsequently released into the cytoplasm
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
A.A. PERMEATIONPERMEATION4.4. ENDOCYTOSISENDOCYTOSIS Permits very large or very lipid-insolublePermits very large or very lipid-insoluble
chemicals to enter the cellchemicals to enter the cell Eg, BEg, B1212 with intrinsic factor and iron with with intrinsic factor and iron with
transferrintransferrin
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
A.A. PERMEATIONPERMEATION5.5. EXOCYTOSISEXOCYTOSIS Reverse processReverse process Expulsion of membrane-encapsulated Expulsion of membrane-encapsulated
material from the cellmaterial from the cell
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
B.B. FICK’S LAW OF DIFFUSIONFICK’S LAW OF DIFFUSION Predicts the movement of molecules across Predicts the movement of molecules across
a barriera barrier Drug absorption is faster in organs with Drug absorption is faster in organs with
larger surface areas (eg, small intestine) larger surface areas (eg, small intestine)
than from organs with smaller absorbing than from organs with smaller absorbing
areas (eg, stomach)areas (eg, stomach)
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
B.B. FICK’S LAW OF DIFFUSIONFICK’S LAW OF DIFFUSION
Drug absorption is faster from organs with Drug absorption is faster from organs with
thin membrane barriers (eg, lungs) than thin membrane barriers (eg, lungs) than
those with thick barriers (eg, skin)those with thick barriers (eg, skin)
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
FICK’S LAW OF DIFFUSIONFICK’S LAW OF DIFFUSION
Area x Permeability coefficientArea x Permeability coefficient
((CC11––CC22) ) X X ______________________________ ______________________________
ThicknessThickness
CC11-higher conc-higher conc
CC22-lower conc-lower conc
Permeability coefficientPermeability coefficient-measure of the mobility -measure of the mobility of the drug in medium of the diffusion pathof the drug in medium of the diffusion pathThicknessThickness-thickness (length of the diffusion path)-thickness (length of the diffusion path)
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
C.C. WATER AND LIPID SOLUBILITY OF WATER AND LIPID SOLUBILITY OF DRUGSDRUGS
1.1. AQUEOUS DIFFUSIONAQUEOUS DIFFUSION Aqueous solubility of a drug is a function of Aqueous solubility of a drug is a function of
the electrostatic charge (degree of ionization,the electrostatic charge (degree of ionization,polarity) of the moleculepolarity) of the molecule
Water molecules are attracted to chargedWater molecules are attracted to charged drug molecules forming an aqueous shell drug molecules forming an aqueous shell
around themaround them Lipid solubility of a molecule is inversely Lipid solubility of a molecule is inversely
proportional to its charge proportional to its charge
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
C.C. WATER AND LIPID SOLUBILITY OF WATER AND LIPID SOLUBILITY OF DRUGSDRUGS
2.2. LIPID DIFFUSIONLIPID DIFFUSION Many drugs are weak bases or weak acidsMany drugs are weak bases or weak acids pH of the medium determines the fraction of pH of the medium determines the fraction of
molecules charged (ionized) versus unchargedmolecules charged (ionized) versus uncharged(nonionized)(nonionized)
Fraction of molecules in the ionized state canFraction of molecules in the ionized state canbe predicted by means of the H-H equation be predicted by means of the H-H equation
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
THE HENDERSON-HASSELBACH EQUATIONTHE HENDERSON-HASSELBACH EQUATION
(protonated)(protonated)
log ___________ = pka - pHlog ___________ = pka - pH
(unprotonated)(unprotonated)
Protonated means associated with a proton Protonated means associated with a proton (a hydrogen ion)(a hydrogen ion)
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
C.C. WATER AND LIPID SOLUBILITY OF WATER AND LIPID SOLUBILITY OF
DRUGS DRUGS 3.3. Ionization of Weak Acids and Weak BasesIonization of Weak Acids and Weak Bases
WEAK BASEWEAK BASE Neutral molecule that can form a cation Neutral molecule that can form a cation
(+ charged) by combining with a proton (+ charged) by combining with a proton (hydrogen ion)(hydrogen ion)
Ionized, more polar, more water soluble Ionized, more polar, more water soluble when they are protonatedwhen they are protonated
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
C.C. WATER AND LIPID SOLUBILITY OF WATER AND LIPID SOLUBILITY OF DRUGSDRUGS
3.3. Ionization of Weak Acids and Weak Bases Ionization of Weak Acids and Weak Bases WEAK ACIDWEAK ACID
Neutral molecule that can reversibly Neutral molecule that can reversibly dissociate into an anion (- charged) and dissociate into an anion (- charged) and
a proton ( hydrogen ion)a proton ( hydrogen ion) Not ionized, less polar, less water solubleNot ionized, less polar, less water soluble when they are protonatedwhen they are protonated
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
RNHRNH33++ RNHRNH22 ++ HH++
protonated weakprotonated weak unprotonated weakunprotonated weak protonproton
base (charged,base (charged, base (uncharged, morebase (uncharged, more
more water-soluble)more water-soluble) lipid-soluble)lipid-soluble)
RCOOHRCOOH RCOORCOO__ ++ H H++
protonated weakprotonated weak unprotonated weakunprotonated weak protonproton
acid (uncharged,acid (uncharged, acid (charged, moreacid (charged, more
more lipid-soluble)more lipid-soluble) water-soluble)water-soluble)
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
The Henderson-Hasselbach EquationThe Henderson-Hasselbach Equation
Clinically important when it is necessaryClinically important when it is necessary
to estimate or alter the partition of drugsto estimate or alter the partition of drugs
between compartments of different pHbetween compartments of different pH
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
The Henderson-Hasselbach EquationThe Henderson-Hasselbach Equation When a patient takes an overdose of a weak When a patient takes an overdose of a weak
acid drug, excretion maybe accelerated by acid drug, excretion maybe accelerated by alkalinizing the urine alkalinizing the urine
Weak acids dissociate to its charged, polar form Weak acids dissociate to its charged, polar form in alkaline urine and cannot readily diffuse back in alkaline urine and cannot readily diffuse back from the renal tubule back to the bloodfrom the renal tubule back to the blood
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
Large number of drugs are weak bases with Large number of drugs are weak bases with amine containing moleculesamine containing molecules
Nitrogen of a neutral amine has 3 atoms Nitrogen of a neutral amine has 3 atoms associated with it plus a pair of unshared associated with it plus a pair of unshared electronselectrons
PrimaryPrimary SecondarySecondary TertiaryTertiary QuaternaryQuaternary
HH R R R R RR
. .. . . . . . . . . . . .. .
R : N : R : NR : N : R : N : R : N :: R : N : R : N : RR : N : R
. .. . . . . . . . . . . .. .
HH H H R R RR
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA. ROUTES OF ADMINISTRATIONA. ROUTES OF ADMINISTRATION Drugs usually enter the body remote from the Drugs usually enter the body remote from the
target tissue or organ and require transport by target tissue or organ and require transport by the circulation to the intended site of actionthe circulation to the intended site of action
BIOAVAILABILITYBIOAVAILABILITY
amount absorbed into the systemic circulationamount absorbed into the systemic circulation amount of drug administeredamount of drug administered
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION
1.1. ORALORAL (swallowed) (swallowed) Maximum convenienceMaximum convenience Absorption maybe slower, and less completeAbsorption maybe slower, and less complete Some drugs have low bioavailability when Some drugs have low bioavailability when
given orallygiven orally
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION
1.1. ORALORAL (swallowed) (swallowed) Subject to Subject to first-pass effectfirst-pass effect (significant amount (significant amount
of the agent is metabolized in the gut wall, of the agent is metabolized in the gut wall, portal circulation, and liver before it reaches portal circulation, and liver before it reaches the systemic circulation)the systemic circulation)
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION
2.2. INTRAVENOUS (IV)/PARENTERALINTRAVENOUS (IV)/PARENTERAL Instantaneous and complete absorptionInstantaneous and complete absorption Bioavailability by definition is 100%Bioavailability by definition is 100% Potentially more dangerous, high blood Potentially more dangerous, high blood
levels reached if administration is too rapidlevels reached if administration is too rapid
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION
3.3. INTRAMUSCULAR (IM)INTRAMUSCULAR (IM) Absorption is often faster and more complete Absorption is often faster and more complete
(higher bioavailability) than oral(higher bioavailability) than oral Large volumes (>5 ml into each buttock) if the Large volumes (>5 ml into each buttock) if the
drug is not irritatingdrug is not irritating
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION
3.3. INTRAMUSCULAR (IM)INTRAMUSCULAR (IM) First-pass effect is avoidedFirst-pass effect is avoided Heparin cannot be given by this route, Heparin cannot be given by this route,
causes bleeding in the musclecauses bleeding in the muscle
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION
4.4. SUBCUTANEOUSSUBCUTANEOUS Slower absorption than IM route Slower absorption than IM route First-pass effect is avoidedFirst-pass effect is avoided Heparin can be given by this route, does Heparin can be given by this route, does
not cause hematomanot cause hematoma
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION
5.5. BUCCAL AND SUBLINGUALBUCCAL AND SUBLINGUAL Buccal routeBuccal route (in the pouch between gums (in the pouch between gums
and cheeks) and cheeks) Permits absorption direct into the systemic Permits absorption direct into the systemic
circulation, bypassing hepatic portal circuit circulation, bypassing hepatic portal circuit and first-pass metabolismand first-pass metabolism
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION
5.5. BUCCAL AND SUBLINGUALBUCCAL AND SUBLINGUAL Slow or fast depending on formulation of Slow or fast depending on formulation of
the productthe product Sublingual routeSublingual route (under the tongue) offers (under the tongue) offers
the same featuresthe same features
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION
6.6. RECTALRECTAL (suppository) (suppository) Partial avoidance of first-pass effect Partial avoidance of first-pass effect
(not completely as the sublingual route)(not completely as the sublingual route) Suppositories tend to migrate upward inSuppositories tend to migrate upward in
the rectum where absorption is partiallythe rectum where absorption is partially
into the portal circulationinto the portal circulation
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION
6.6. RECTAL RECTAL (suppository)(suppository) Larger amounts of unpleasant drugs Larger amounts of unpleasant drugs
are better administered rectallyare better administered rectally May cause significant irritationMay cause significant irritation
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION
7.7. INHALATIONINHALATION For respiratory diseasesFor respiratory diseases Delivery closest to the target tissueDelivery closest to the target tissue Results into rapid absorption because of Results into rapid absorption because of
the rapid and thin alveolar surface areathe rapid and thin alveolar surface area
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION
7.7. INHALATION INHALATION Drugs that are gases at room temperature Drugs that are gases at room temperature
(eg, nitrous oxide), or easily volatilized (eg, nitrous oxide), or easily volatilized (anesthetics) (anesthetics)
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION
8.8. TOPICAL TOPICAL Application to the skin or mucous membraneApplication to the skin or mucous membrane
of the eye, nose, throat, airway, or vagina of the eye, nose, throat, airway, or vagina
for local effectfor local effect
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION
8.8. TOPICAL TOPICAL Rate of absorption varies with the areaRate of absorption varies with the area
of application and drug’s formulationof application and drug’s formulation Absorption is slower compared to other Absorption is slower compared to other
routesroutes
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION
9.9. TRANSDERMAL TRANSDERMAL Application to the skin for systemic effect Application to the skin for systemic effect Rate of absorption occurs very slowlyRate of absorption occurs very slowly First-pass effect is avoidedFirst-pass effect is avoided
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSB.B. BLOOD FLOWBLOOD FLOW Influences absorption from IM, subcutaneous, Influences absorption from IM, subcutaneous,
and in shock and in shock High blood flow maintains a high drug depot-High blood flow maintains a high drug depot-
to-blood concentration gradientto-blood concentration gradient Maximizes absorptionMaximizes absorption
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ABSORPTION OF DRUGSABSORPTION OF DRUGSC.C. CONCENTRATIONCONCENTRATION Concentration gradient Concentration gradient Major determinant of the rate of absorption Major determinant of the rate of absorption
(Fick’s law)(Fick’s law)
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DISTRIBUTION OF DRUGSDISTRIBUTION OF DRUGSA.A. DETERMINANTS OF DISTRIBUTIONDETERMINANTS OF DISTRIBUTION
1.1. Size of the organSize of the organ Size of the organ determines the concentrationSize of the organ determines the concentration
gradient between blood and the organ gradient between blood and the organ Eg, skeletal muscle and brainEg, skeletal muscle and brain
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DISTRIBUTION OF DRUGSDISTRIBUTION OF DRUGSA.A. DETERMINANTS OF DISTRIBUTIONDETERMINANTS OF DISTRIBUTION
2.2. Blood flowBlood flow Important determinant of the rate of uptakeImportant determinant of the rate of uptake Well-perfused organs Well-perfused organs
BrainBrain Heart, kidneys Heart, kidneys Splanchnic organsSplanchnic organs
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DISTRIBUTION OF DRUGSDISTRIBUTION OF DRUGSA.A. DETERMINANTS OF DISTRIBUTIONDETERMINANTS OF DISTRIBUTION
3.3. SolubilitySolubility If the drug is very soluble in cells, the If the drug is very soluble in cells, the
concentration in the perivascular space concentration in the perivascular space
will be lower and diffusion from the vessel will be lower and diffusion from the vessel
into the extravascular tissue will be facilitatedinto the extravascular tissue will be facilitated
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
DISTRIBUTION OF DRUGSDISTRIBUTION OF DRUGSA.A. DETERMINANTS OF DISTRIBUTIONDETERMINANTS OF DISTRIBUTION
4.4. BindingBinding Binding of drugs to macromolecules in Binding of drugs to macromolecules in
the blood or tissue compartment will tend the blood or tissue compartment will tend
to increase the drug’s concentration in thatto increase the drug’s concentration in that
compartmentcompartment
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
DISTRIBUTION OF DRUGSDISTRIBUTION OF DRUGSB.B. APPARENT VOLUME OF DISTRIBUTIONAPPARENT VOLUME OF DISTRIBUTION
VVdd
Amount of drug in the body to the Amount of drug in the body to the concentration in the plasmaconcentration in the plasma
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METABOLISM OF DRUGSMETABOLISM OF DRUGSA.A. AS MECHANISM OF TERMINATION OF AS MECHANISM OF TERMINATION OF
DRUG ACTIONDRUG ACTION Action of many drugs is terminated before theyAction of many drugs is terminated before they
are excretedare excreted Metabolized to biologically inactive derivativesMetabolized to biologically inactive derivatives Conversion to a metabolite is a form of Conversion to a metabolite is a form of
eliminationelimination
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
METABOLISM OF DRUGSMETABOLISM OF DRUGSB.B. AS MECHANISM OF DRUG ACTIVATIONAS MECHANISM OF DRUG ACTIVATION
PRODRUGSPRODRUGS Inactive as administered and must beInactive as administered and must be
metabolized in the body to become active metabolized in the body to become active Eg, levodopa, minoxidilEg, levodopa, minoxidil
Many drugs are active as administeredMany drugs are active as administered
and have active metabolites as well and have active metabolites as well Some benzodiazepinesSome benzodiazepines
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
METABOLISM OF DRUGSMETABOLISM OF DRUGSC.C. DRUG ELIMINATION WITHOUT DRUG ELIMINATION WITHOUT
METABOLISMMETABOLISM Drugs not modified by the bodyDrugs not modified by the body Continue to act until they are excretedContinue to act until they are excreted Eg, lithiumEg, lithium
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ELIMINATION OF DRUGSELIMINATION OF DRUGSDeterminants of the duration of action for most Determinants of the duration of action for most
drugsdrugs DosageDosage Rate of elimination following the last dose Rate of elimination following the last dose
Disappearance of the active molecules Disappearance of the active molecules
from from the bloodstreamthe bloodstream
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ELIMINATION OF DRUGSELIMINATION OF DRUGS Drug elimination is not the same as drug Drug elimination is not the same as drug
excretionexcretion A drug maybe eliminated by metabolism A drug maybe eliminated by metabolism
long before the modified molecules are long before the modified molecules are
excreted from the bodyexcreted from the body
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ELIMINATION OF DRUGSELIMINATION OF DRUGS For most drugsFor most drugs, excretion is by way of the , excretion is by way of the
kidneys (except anesthetic gases-lungs)kidneys (except anesthetic gases-lungs) For drugs with active metabolitesFor drugs with active metabolites
(eg, diazepam), elimination of the parent (eg, diazepam), elimination of the parent
molecule by metabolism is not synonymousmolecule by metabolism is not synonymous
with termination of actionwith termination of action For drugs that are not metabolizedFor drugs that are not metabolized, excretion, excretion
is the mode of eliminationis the mode of elimination
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ELIMINATION OF DRUGSELIMINATION OF DRUGS A small number of drugsA small number of drugs combine irreversibly combine irreversibly
with their receptors, disappearance from thewith their receptors, disappearance from thebloodstream is not equivalent to cessation of bloodstream is not equivalent to cessation of drug actiondrug action
Very prolonged actionVery prolonged action Eg, phenoxybenzamine, irreversible inhibitor Eg, phenoxybenzamine, irreversible inhibitor
of alpha receptors is eliminated from the of alpha receptors is eliminated from the bloodstream in 1 h or less after administration,bloodstream in 1 h or less after administration,drug’s action lasts for 48 h drug’s action lasts for 48 h
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ELIMINATION OF DRUGSELIMINATION OF DRUGSA.A. FIRST ORDER ELIMINATIONFIRST ORDER ELIMINATION Rate of elimination is proportionate to the Rate of elimination is proportionate to the
concentration (ie, the higher the concentration, concentration (ie, the higher the concentration, the greater the amount eliminated per unit the greater the amount eliminated per unit time)time)
Drug’s concentration in plasma decreases Drug’s concentration in plasma decreases exponentially with timeexponentially with time
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ELIMINATION OF DRUGSELIMINATION OF DRUGSA.A. FIRST ORDER ELIMINATIONFIRST ORDER ELIMINATION Half-life of elimination is constant regardlessHalf-life of elimination is constant regardless
of amount of drug in the bodyof amount of drug in the body Concentration of such drug in the blood will Concentration of such drug in the blood will
decrease by 50% for every half-lifedecrease by 50% for every half-life Most common processMost common process Followed by most drugs Followed by most drugs
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
FIRST ORDER KINETICSFIRST ORDER KINETICS
Plasma conc.(Cp)
Time (h)
2.5 units/h
1.25 units/h
5 units/h5 units/h
ELIMINATION OF DRUGSELIMINATION OF DRUGSB.B. ZERO ORDER ELIMINATIONZERO ORDER ELIMINATION Rate of elimination is constant regardless Rate of elimination is constant regardless
of concentrationof concentration Occurs with drugs that saturate theirOccurs with drugs that saturate their
elimination of mechanism at concentrations elimination of mechanism at concentrations
of clinical interestof clinical interest
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ELIMINATION OF DRUGSELIMINATION OF DRUGSB.B. ZERO ORDER ELIMINATIONZERO ORDER ELIMINATION Concentration of such drugs in plasma Concentration of such drugs in plasma
decrease in linear fashion over timedecrease in linear fashion over time With higher doses, there will be bigger With higher doses, there will be bigger
chances of toxic effect because the patientchances of toxic effect because the patient
may not be able to eliminate itmay not be able to eliminate it Eg, alcohol, phenytoin, aspirinEg, alcohol, phenytoin, aspirin
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology
ZERO-ORDER KINETICSZERO-ORDER KINETICS
2.5 units/h
Plasma conc.(Cp)
Time (h)
2.5 units/h
2.5 units/h